Cell stem cell, 2011-12, Vol.9 (6), p.575-587
2011
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- Autor(en) / Beteiligte
- Titel
- The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner
- Ist Teil von
- Cell stem cell, 2011-12, Vol.9 (6), p.575-587
- Ort / Verlag
- Cambridge, MA: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the Ink4/Arf locus. Jhdm1b also cooperates with Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming. [Display omitted] ► Vitamin C reduces H3K36me2/3 levels through the demethylases Jhdm1a/1b ► Jhdm1a/1b enhance somatic cell reprogramming ► Jhdm1b and vitamin C suppress senescence and enhance cell proliferation ► Jhdm1b cooperates with Oct4 to activate the microRNA 302/367 cluster
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1934-5909eISSN: 1875-9777DOI: 10.1016/j.stem.2011.10.005Titel-ID: cdi_proquest_miscellaneous_908739548
- Format
- –
- Schlagworte
- Animals, Antioxidants - pharmacology, Ascorbic Acid - pharmacology, Biological and medical sciences, Cell Cycle - physiology, Cell differentiation, maturation, development, hematopoiesis, Cell physiology, Cells, Cultured, Cellular Reprogramming - drug effects, Cellular Senescence - physiology, F-Box Proteins - genetics, F-Box Proteins - metabolism, Fibroblasts - cytology, Fibroblasts - physiology, Fundamental and applied biological sciences. Psychology, Histones - genetics, Histones - metabolism, Humans, Jumonji Domain-Containing Histone Demethylases - genetics, Jumonji Domain-Containing Histone Demethylases - metabolism, Lysine - metabolism, Mice, Mice, Transgenic, Molecular and cellular biology, Octamer Transcription Factor-3 - genetics, Octamer Transcription Factor-3 - metabolism, Pluripotent Stem Cells - cytology, Pluripotent Stem Cells - physiology